The construction of water-soluble synthetic hosts with a stimuli-responsive endo-functionalized cavity is challenging. These hosts feature a switchable cavity and may bring new properties to the ...fields of self-assembly, molecular machines, and biomedical sciences. Herein, we report a pair of water-soluble naphthotubes with a pH-responsive endo-functionalized cavity. The inward-directing secondary amine group of the hosts can be protonated and deprotonated. Thus, the hosts have different cavity features at the two states and show drastically different binding preference and selectivity in water. We reveal that the binding difference of the two host states is originated from the differences in charge repulsion, hydrogen bonding and the hydrophobic effects. Moreover, the guest binding can be easily switched in a ternary mixture with two guest molecules by adjusting the pH value of the solution. These pH-responsive hosts may be used for the construction of smart self-assembly systems and water-soluble molecular machines.
Tumor-associated macrophages (TAMs) have been linked to promoting tumor progression by stimulating angiogenesis, cell growth and inflammation. NFKB activity in TAMs may mediate ...inflammation-associated tumor formation. However, most isolated TAMs from established tumors express a M2 phenotype with less NFKB activation and show a strong immunosuppressive phenomenon. How tumors affect the dynamic of NFKB activity in TAMs, and hence maintain their pro-tumor M2 phenotype is still poorly understood. We recently found that hepatoma-derived toll-like receptor 2 (TLR2)-related ligands are capable of stimulating M2 macrophage differentiation via controlling NFKB RELA/p65 protein homeostasis by selective autophagy. TLR2 signal induces NFKB RELA cytosolic ubiquitination and leads to its degradation by SQSTM1/p62-mediated autophagy. Inhibition of autophagy will rescue NFKB activity and shape the phenotype of hepatoma-polarized M2 macrophages. This suggests that autophagy might play a role in manipulating TAM functions and tumor-associated immune responses. Our study also demonstrates that autophagy can directly control a transcriptional factor in addition to its regulatory molecules. This finding uncovers a new role of autophagy in controlling cellular functions.
Buried salt bridges widely exist in protein structures but are rarely used in synthetic systems for molecular recognition in water. By mimicking the binding pocket of bioreceptors, we designed and ...synthesized a pair of endo‐functionalized macrocyclic hosts with secondary ammonium groups in a hydrophobic cavity. We found that these macrocycles are able to selectively recognize carboxylic acids in water through salt bridges and the hydrophobic effect. Moreover, it was demonstrated that these macrocyclic receptors can be used in circular‐dichroism‐based optical chirality sensing of chiral carboxylic acids and fluorescent sensing of phenylpyruvic acid—a biomarker for phenylketonuria. This research showcases that buried salt bridges can be effectively used by endo‐functionalized macrocyclic hosts for molecular recognition in water, where solvent screening on polar noncovalent interactions is high.
Buried salt bridges can be effectively used by a pair of endo‐functionalized macrocyclic hosts for the selective recognition of functional carboxylic acids in water, where solvent screening on polar noncovalent interactions is high.
Self-gravity calculations for 3D are expensive in terms of computational time. Several methods exist for this computation, for example multigrid and spectral methods. Unfortunately, these approaches ...require the imposition of boundary conditions, which can be either numerically expensive (direct Newtonian sums), artificial (periodicity assumptions), or potentially imprecise (multipolar expansions). In this work we present a novel direct numerical method to calculate the gravitational potential and forces by solving the Poisson equation without the need to prescribe artificial boundary conditions; this method, despite being direct, turns out to be efficient due to the possibility of using a fast Fourier transform for its implementation. For a grid having N zones in each dimension, the computational complexity of the method presented here is , which is comparable with multigrid methods under no consideration of boundary settings. Finally, a numerical study shows this proposed method can achieve second order for calculations of both potential and forces.
Yen et al. advanced a direct approach for the calculation of self-gravitational force to second-order accuracy based on uniform grid discretization. This method improves the accuracy of N-body ...calculation using exact integration of kernel functions and employing the Fast Fourier Transform to reduce the complexity of computation to be nearly linear. This direct approach is free of artificial boundary conditions; however, the applicability is limited by the uniform discretization of grids. We report here an advancement in the direct method with the implementation of adaptive mesh refinement and maintaining second-order accuracy, which breaks the barrier set by uniform grid discretization. The adoption of graphic process units can significantly speed up the computation and make application of this method possible for the astrophysical systems of gaseous disk galaxies and protoplanetary disks.
Abstract Background The optimal dosage and timing of tranexamic acid (TXA) in total knee arthroplasty (TKA) are undetermined. The purpose of this study was to explore the effect of multiple boluses ...of intravenous TXA on hidden blood loss (HBL), inflammatory response, and knee function after primary TKA without tourniquet. Methods A total of 151 patients were randomly divided into 3 groups to receive single bolus of 20 mg/kg IV-TXA before skin incision (group A), or another bolus of 10 mg/kg IV-TXA 3 hours later (group B), or another 2 boluses of 10 mg/kg IV-TXA 3 hours and 6 hours later (group C). TKAs without tourniquet were operated by 1 single surgeon. The primary outcomes were HBL and maximum hemoglobin drop. Other outcome measurements such as total blood loss, transfusion rate, inflammation markers (C-reactive protein, interleukin 6), visual analog scale pain score, limb swelling ratio, Hospital for Surgery Score, range of motion, length of hospital stay (LOH), and deep venous thrombosis were also compared. Results The mean HBL and maximum Hb drop in group C (467.6 ± 305.9 and 20.9 ± 9.3) was lower than those in group A (763.0 ± 373.3, P < .001; 28.7 ± 12.2, P < .001) and group B (637.5 ± 303.5, P = .010; 25.2 ± 8.4, P = .036). However, such differences were not detected between groups A and B ( P = .058 and P = .080, respectively). The mean value of total blood loss in the groups A, B, and C were 967.2 ± 380.1, 803.7 ± 321.8, and 677.6 ± 326.0 mL, respectively, with a significant intergroup difference ( P < .001). The mean serum level of C-reactive protein and interleukin 6 in group C were lower than those in group A and group B on postoperative days 1 and 2. The visual analog scale pain score and swelling ratio were also lower in group C than in the other 2 groups with statistical significance on POD 1-3. Moreover, the Hospital for Surgery Score, range of motion, and LOH were better in group C. No episodes of transfusion or deep venous thrombosis had occurred. Conclusion Multiple boluses of IV-TXA can effectively reduce HBL after primary TKA without tourniquet. What is the most important is that, by adding another bolus of IV-TXA, patients can gain a smaller decline of Hb, less postoperative inflammatory response, less pain, less knee swelling, better knee function, and shorter LOH.
The maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment is converted to an environment of embryonic-driven development through dramatic ...reprogramming. However, how maternally supplied transcripts are dynamically regulated during MZT remains largely unknown. Herein, through genome-wide profiling of RNA 5-methylcytosine (m5C) modification in zebrafish early embryos, we found that m5C-modified maternal mRNAs display higher stability than non-m5C-modified mRNAs during MZT. We discovered that Y-box binding protein 1 (Ybx1) preferentially recognizes m5C-modified mRNAs through π-π interactions with a key residue, Trp45, in Ybx1’s cold shock domain (CSD), which plays essential roles in maternal mRNA stability and early embryogenesis of zebrafish. Together with the mRNA stabilizer Pabpc1a, Ybx1 promotes the stability of its target mRNAs in an m5C-dependent manner. Our study demonstrates an unexpected mechanism of RNA m5C-regulated maternal mRNA stabilization during zebrafish MZT, highlighting the critical role of m5C mRNA modification in early development.
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•RNA-BisSeq revealed a dynamic RNA m5C landscape during zebrafish embryogenesis•Ybx1 preferentially recognizes m5C-modified mRNAs•Ybx1 deficiency leads to early gastrulation defects in zebrafish embryos•Ybx1 and Pabpc1a coordinately regulate m5C-modified maternal mRNA stability
RNA modifications exert important effects in many critical physiological processes. Using RNA-BisSeq, Yang et al. provide a comprehensive view of the RNA m5C landscape in zebrafish early embryos and show that m5C-modified maternal mRNAs are stabilized by Ybx1 and Pabpc1a during zebrafish MZT.
Benzene hydrogenation is an important industrial process. The reaction is incomplete, resulting in a mixture of benzene, cyclohexane, and/or cyclohexene that have to be separated before any further ...reactions. The currently used extractive and azeotropic distillations are operationally complex and energy intensive. Adsorptive separation provides an alternative energy‐efficient method. However, the separation of the ternary mixture by adsorptive separation has not yet been reported. In the present research, we report two macrocyclic hosts with hydrogen‐bonding sites in their cavities that are able to separate the ternary mixture of benzene, cyclohexene, and cyclohexane. N−H⋅⋅⋅π interactions were found to play a key role in the selective separation. In addition, fast adsorption, high loading ratios, and easy recycling are achieved with the present system, which is promising for practical applications.
Mixtures of benzene, cyclohexene, and cyclohexane can be separated through solid‐vapor adsorption by using the activated solids of amide naphthotubes. N−H⋅⋅⋅π interactions are found to play a key role in the adsorption selectivity among the three structurally similar molecules.
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